The technical field of this invention concerns methods and systems for encapsulating living cells for the production of biologically active factors.
There is considerable interest at present in the biologically active products of living cells, including, for example, neurotransmitters, hormones, cytokines, nerve growth factors, angiogenesis factors, blood coagulation factors, lymphokines, enzymes and other therapeutic agents. There is also substantial interest in developing new methods and systems for producing such biological factors as well as in delivering these factors to subjects for therapeutic purposes.
For example, Parkinson's disease is characterized by the degeneration of the dopaminergic nigrostriatal system. Striatal implantation of polymer rods which release sustained amounts of a neurotransmitter, dopamine, has been reported to alleviate experimental Parkinsonism in rodents, indicating that the release of dopamine alone in the proper target structure may be able to correct this functional deficiency.
In contrast to the limited capacity of a polymeric matrix drug release system, encapsulated dopamine-releasing cells have been proposed as a means to provide a continuous supply of neurotransmitters. The encapsulation of neurotransmitter-secreting cells by a permselective membrane which permits diffusion of the biological factor may not only prohibit the escape of mitotically active cells, but also prevent host rejection in the case of cross-species transplantation.
A number of researchers have proposed the use of microcapsules--tiny spheres which encapsulate a microscopic droplet of a cell solution--for both therapeutic implantation purposes and large scale production of biological products. However, there are a number of shortcomings to the microencapsulation approach: the microcapsules can be extremely difficult to handle (and retrieve, after implantation); their volume is limited; and the types of encapsulating materials which can be used are constrained (by the formation process) to polymers which can dissolve in biocompatible solvents.
An alternative approach has been macroencapsulation, which typically involves loading cells into hollow fibers and then closing the extremities at both ends with a polymer glue. In contrast to microcapsules, macrocapsules offer the advantage of easy retrievability, an important feature in therapeutic (especially, neural) implants. However, the construction of macrocapsules in the past has often been tedious and labor intensive. Moreover, due to unreliable closure, conventional methods of macroencapsulation have provided inconsistent results.
There exists a need for better techniques for macroencapsulation of cells for both therapeutic implantation and industrial production purposes. Encapsulation techniques which can be practiced in a an automated fashion, and which permit the usage of a wider range of materials and/or provide more reliable closure would satisfy a long felt need in the art.